Subcutaneous Tarlatamab Safe, Active Against ES-SCLC Tumors in Phase 1B Trial

Subcutaneous 15 mg tarlatamab demonstrated consistent tolerability and preliminary antitumor activity in a phase 1B trial assessing the agent in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC), according to new data presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) in Seoul this week.¹

The DeLLphi-308 trial (NCT06598306), presented by primary author Pedro Rocha, MD, PhD, of Vall d’Hebron University Hospital and Institute of Oncology, showed the subcutaneous administration of the bispecific T-cell engager (BiTE) immunotherapy may produce delayed lower peak serum concentrations compared with intravenous (IV) regimens. This may reduce the frequency or severity of adverse events including cytokine release syndrome (CRS) among patients receiving immunotherapy for ES-SCLC.

Investigators additionally noted the improved convenience of subcutaneous administration versus standard intravenous.

“The findings from DeLLphi-308 suggest that 15 mg subcutaneous tarlatamab dose can achieve serum exposures comparable to the approved 10 mg intravenous dosing administered every 2 weeks while maintaining a favorable safety profile,” Rocha said in a statement accompanying the new data.² “The predominantly low-grade CRS events and preliminary antitumor activity support continued investigation of this more convenient route of administration.”

DeLLphi-308 Design

The open-label, multicenter, dose-exploration and expansion trial served as the first clinical evaluation of subcutaneous tarlatamab.¹ The team enrolled patients with ES-SCLC that either progressed or recurred after ≥1 platinum-based chemotherapy.

Investigators first assessed subcutaneous tarlatamab at target doses of 10 and 15 mg — administered bi-weekly — in cohorts of 20 patients each. They selected the 15 mg dose after it achieved exposures comparable to the established IV 10 mg dose; patients were no longer monitored for post-dose C1D1 and C1D8 after the optimal dose selection.

Promising Early-Stage Outcomes

Rocha reported outcomes of 60 participants to receive subcutaneous tarlatamab in DeLLphi-308 at WCLC 2026. Mean patient age was 65 years old (range, 48 – 83). Patients primarily received 2 lines of therapy previously (37%); 88% had prior anti-PD(L1) therapy. Rates of patients with brain and liver metastases were 48% and 42%, respectively.

Just 13% (n = 8) of all treated patients reported a grade ≥3 treatment-related adverse event (TRAE); 12% (n = 7) experienced a dose interruption due to subcutaneous tarlatamab and only 1 patient discontinued therapy. No fatal outcomes were associated with the subcutaneous regimen.

The team further reported that 15 mg subcutaneous tarlatamab was associated with lower rates of CRS compared to the 10 mg IV regimen. Just 11 patients reported a grade 1 CRS (28%); another 4 (10%) reported a grade 2 CRS, and none reported grade ≥3.

Regarding anticancer activity, investigators observed a 30% objective response rate (ORR) in previously treated ES-SCLC. Median progression-free survival was 3.7 months among patients treated with 15 mg dose (95% CI, 1.9 – 7.0), and median overall survival was 11.7 months.

Supported by the promising dose-finding data presented at WCLC 2026, a phase 3 trial (DeLLphi-315 [NCT07778316]) is underway to assess the efficacy and safety of subcutaneous tarlatamab compared with an IV regimen in patients with small-cell lung cancer. Primary completion of DeLLphi-315 is projected for September 2027.³

References

1. Rocha P, Paz-Ares L, Mark M, Markman B, et al. Subcutaneous (SC) Tarlatamab in Patients With Extensive-Stage Small Cell Lung Cancer (ES-SCLC): DeLLphi-308 Phase 1b Study. Presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC). Seoul, SK. September 12 – 15, 2026.
2. Subcutaneous Tarlatamab Shows Favorable Safety Profile and Antitumor Activity in Extensive-Stage Small Cell Lung Cancer. News release. International Association for the Study of Lung Cancer. September 12, 2026. Accessed September 12, 2026.
3. Phase 3 Trial of Tarlatamab (SC vs IV) in Extensive-Stage Small Cell Lung Cancer After Platinum Based First-line Chemotherapy (ES-SCLC) (DeLLphi-315). ClinicalTrials.gov. Accessed September 12, 2026. Updated August 21, 2026. https://clinicaltrials.gov/study/NCT07778316